Key information relevant to the recruitment process for the
overall study, such as dates of the recruitment period and locations

People with hepatitis C virus (HCV)/HIV coinfection were recruited for participation in this study.

Pre-Assignment Details

Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

330 subjects were to receive 12 weeks of PEG+RBV to determine EVR status. Of the 330, 33 discontinued prior to week 12; 113 were non-EVRs, 80 of whom were randomized between Arms A and B; and 184 achieved EVR, 170 of whom were eligible to continue. 169 of the 170 were assigned to Arm C and one was inadvertently randomized between Arms A and B.

Reporting Groups

Description

Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & ribavirin [RBV] 1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

No text entered.

Reporting Groups

Description

Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & ribavirin [RBV] 1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

SCMFS is the difference between the Metavir fibrosis scores of the study exit and study entry liver biopsies where the difference is scaled to one year. The SCMFS assesses the annualized change in the severity of liver fibrosis on a continuous scale from -4.0 Metavir units per year (reduced fibrosis over time, a positive study outcome) to +4.0 Metavir units per year (increased fibrosis over time).

Time Frame

Baseline and at week 72 or premature discontinuation

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

62 Arm A and B participants who had follow-up liver biopsy performed or those who had Week 72 potential as of May 2, 2007 but no follow-up liver biopsy. In the unadjusted ITT analysis, the participants without SCMFS available were assigned the highest SCMFS (+2).

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Additional details about the analysis, such as null hypothesis and power calculation:

Accrual and follow-up on Arms A and B were halted for futility at the first independent interim review of the primary endpoint conducted on May 2, 2007.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

No text entered.

[3]

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

P-value is pre-specified 1-sided test that PEG slows liver fibrosis progression. Accrual and follow-up on Arms A and B were halted at interim review for lack of fibrosis progression in Arm B (control arm). P-value is unadjusted for interim analysis.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

All Arm A, B and C participants

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Liver biopsies were performed within 42 days prior to randomization between Arms A and B while the participant remained on PEG-IFN plus RBV (=entry biopsy) and again at week 72 or premature study discontinuation (=exit biopsy). SCIIS was defined as the difference between the Ishak inflammation score of the exit biopsy and the Ishak inflammation score of the entry biopsy, where the difference is scaled to one year.

Time Frame

Baseline and at week 72 or premature discontinuation

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

All participants with SCIIS available (Complete Cases)

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

All Arm A, B and C participants

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Measured Values

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Number of Participants Analyzed
[units: participants]

44

42

169

Number of Participants With Anemia
[units: Participant]

Anemia >= Grade 2

1

0

6

Grade 2

0

0

3

Grade 3

0

0

1

Grade 4

1

0

2

No statistical analysis provided for Number of Participants With Anemia

5. Secondary:

Number of Participants With Neutropenia [ Time Frame: Up to 96 weeks ]

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

All Arm A, B and C participants

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Measured Values

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Number of Participants Analyzed
[units: participants]

44

42

169

Number of Participants With Neutropenia
[units: Participant]

Neutropenia >= Grade 2

20

10

96

Grade 2

7

4

38

Grade 3

10

5

37

Grade 4

3

1

21

No statistical analysis provided for Number of Participants With Neutropenia

6. Secondary:

Number of Participants With Thrombocytopenia [ Time Frame: Up to 96 weeks ]

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

All Arm A, B and C participants

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Measured Values

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Number of Participants Analyzed
[units: participants]

44

42

169

Number of Participants With Thrombocytopenia
[units: Participant]

Thrombocytopenia >= Grade 2

14

4

31

Grade 2

10

3

25

Grade 3

4

1

5

Grade 4

0

0

1

No statistical analysis provided for Number of Participants With Thrombocytopenia

7. Secondary:

Number of Participants With Depression and/or Other Psychological Events [ Time Frame: Up to 96 weeks ]

Measure Type

Secondary

Measure Title

Number of Participants With Depression and/or Other Psychological Events

Measure Description

Depression and other psychological events. DAIDS Toxicity Grading Table (1992) was used for grading. The protocol required reporting of depression and other psychological events of Grade 3 or higher or if led to a change in treatment, regardless of grade.

Time Frame

Up to 96 weeks

Safety Issue

Yes

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

All Arm A, B and C participants

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Measured Values

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Number of Participants Analyzed
[units: participants]

44

42

169

Number of Participants With Depression and/or Other Psychological Events
[units: Participant]

Any psychological

3

1

19

Grade 3

2

1

18

Grade 4

1

0

1

No statistical analysis provided for Number of Participants With Depression and/or Other Psychological Events

8. Secondary:

Other High-grade Signs and Symptoms and Laboratory Values [ Time Frame: Up to 96 Weeks ]

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

All Arm A, B and C participants

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Measured Values

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Number of Participants Analyzed
[units: participants]

44

42

169

Other High-grade Signs and Symptoms and Laboratory Values
[units: Participant]

Any Other

22

20

84

Grade 3

15

15

73

Grade 4

7

5

11

No statistical analysis provided for Other High-grade Signs and Symptoms and Laboratory Values

9. Secondary:

Number of Participants With Dose Modifications, Temporary Stops, and Premature Treatment Discontinuations [ Time Frame: Up to 96 Weeks ]

Measure Type

Secondary

Measure Title

Number of Participants With Dose Modifications, Temporary Stops, and Premature Treatment Discontinuations

Measure Description

3-level categorical of the worst of 1) premature treatment discontinuation, 2) temporary stop or 3) dose reduction. For Arm C, the worst for either PEG-IFN or RBV is summarized.

Time Frame

Up to 96 Weeks

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

All Arm A and C participants. Arm B participants did not receive treatment.

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

A categorical variable with levels adherent and non-adherent based on participants' self report. For Arm A, adherence was defined as not missing PEG within 2 weeks of visit. For Arm C, adherence was defined as not missing any PEG within 2 weeks of visit and not missing RBV within 4 days of visit.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

All Arm A and Arm C participants. Arm B participants did not receive treatment.

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Measured Values

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Number of Participants Analyzed
[units: participants]

44

0

159

Number of Participants Adherent to Study Medications
[units: Participant]

Week 0: Number of participants with adherence data

0

158

Week 0: Number of participants adherent to meds

NA
[1]

132

Week 12:Number of participants with adherence data

37

150

Week 12:Number of participants adherent to meds

32

125

Week 24:Number of participants with adherence data

32

145

Week 24:Number of participants adherent to meds

28

118

Week 48:Number of participants with adherence data

22

120

Week 48:Number of participants adherent to meds

19

95

Week 60:Number of participants with adherence data

0

91

Week 60:Number of participants adherent to meds

NA
[1]

79

Week 72:Number of participants with adherence data

8

0

Week 72:Number of participants adherent to meds

7

NA
[1]

[1]

Evaluation not specified in protocol at this timepoint.

No statistical analysis provided for Number of Participants Adherent to Study Medications

Number of Participants With Undetectable HIV Viral Load (<50 Copies/mL)

Measure Description

A blood sample was drawn to determine the HIV-1 viral load. HIV-1 viral load was categorized as <50 copies/mL (undetectable) or >=50 copies/mL (detectable). 50 is the lower limit of detection of the assay.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

All Arm A, B, and C participants

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

All Arm A, B and C participants

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Measured Values

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Number of Participants Analyzed
[units: participants]

44

42

169

Sustained Virologic Response
[units: Participant]

Yes

0

0

88

No

44

42

81

No statistical analysis provided for Sustained Virologic Response

13. Secondary:

Use of Antianorexia Agents, Such as Megestrol and Dronabinol [ Time Frame: Up to 96 weeks ]

Measure Type

Secondary

Measure Title

Use of Antianorexia Agents, Such as Megestrol and Dronabinol

Measure Description

Use of antianorexia agents, such as megestrol and dronabinol at any time after pre-assignment.

Time Frame

Up to 96 weeks

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

All Arm A, B and C participants

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Measured Values

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Number of Participants Analyzed
[units: participants]

44

42

169

Use of Antianorexia Agents, Such as Megestrol and Dronabinol
[units: Participant]

Number of participants who used megestrol

2

1

6

Number of participants who used dronabinol

4

4

22

No statistical analysis provided for Use of Antianorexia Agents, Such as Megestrol and Dronabinol

14. Secondary:

Prescription as Needed of Erythropoietin (EPO), Granulocyte Colony-stimulating Factor (GCSF), and Granulocyte-monocyte Colony-stimulating Factor (GM-CSF) [ Time Frame: At any time after pre-assignment ]

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

All Arm A, B and C participants

Reporting Groups

Description

A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.

B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)

At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.

C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts
the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release
and can embargo communications regarding trial results for a period that is less than or equal to 60 days.
The sponsor cannot require changes to the communication and cannot extend the embargo.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release
and can embargo communications regarding trial results for a period that is more than 60 days but less than
or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Restriction Description:
In accordance with the Clinical Trial Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve US or foreign patent or other intellectual property rights.